Azacitidine

Azacitidine is a pyrimidine nucleoside analog of cytidine. It is incorporated into DNA and RNA, inhibiting DNA methyltransferases, leading to DNA hypomethylation and re-expression of tumor suppressor genes. It also has direct cytotoxic effects on abnormal hematopoietic cells. The injectable form is given at 75 mg/m² subcutaneously or intravenously for 7 days. The oral form (300 mg) is used as maintenance therapy for AML.

• Myelodysplastic Syndromes (MDS): Refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL)
• Acute Myeloid Leukemia (AML) - maintenance therapy in adult patients who achieved complete remission after induction therapy

Azacitidine is a pyrimidine nucleoside analog that inhibits DNA and RNA methyltransferases. After cellular uptake, it is converted to nucleotide triphosphates and incorporated into DNA and RNA.

Incorporation into DNA inhibits DNA methyltransferases, reducing DNA methylation and altering gene expression, including re-expression of tumor suppressor genes. Incorporation into RNA inhibits RNA methyltransferases, reducing RNA stability and protein synthesis.

Azacitidine inhibits DNA methyltransferases, causing DNA hypomethylation, which leads to re-expression of tumor suppressor genes and induces differentiation and apoptosis of abnormal cells. It also exerts direct cytotoxicity on rapidly dividing cancer cells.

Injection (MDS): 75 mg/m², subcutaneous or intravenous infusion, daily for 7 days, 28-day cycle; may increase to 100 mg/m² after 2 cycles if no benefit and no severe toxicity.

Oral Tablet (AML maintenance): 300 mg once daily, 14 days on treatment and 14 days off (28-day cycle).

Injection: Administered by a healthcare professional via subcutaneous or intravenous infusion.

Oral Tablet: Take with or without food. Do not split, crush, or chew the tablet.

If a dose is missed, take it as soon as possible on the same day and resume normal schedule the next day. Do not take 2 doses on the same day. If a dose is vomited, do not take another dose on the same day.

• Nausea
• Anemia
• Thrombocytopenia
• Vomiting
• Pyrexia
• Leukopenia
• Diarrhea
• Injection site erythema
• Constipation
• Neutropenia
• Ecchymosis
• Fatigue
• Headache
• Dizziness
• Insomnia
• Rash
• Pruritus
• Anorexia
• Abdominal pain
• Arthralgia
• Back pain
• Cough
• Nasopharyngitis

• Caution in hepatic or renal impairment
• May cause fetal harm during pregnancy
• Females of reproductive potential should use effective contraception during treatment and for 6 months after the last dose
• Male patients should also use contraception during treatment
• Avoid use during breastfeeding

• Severe hypersensitivity to azacitidine or mannitol
• Advanced malignant hepatic tumors

No formal clinical drug interaction studies have been conducted. In vitro studies indicate that azacitidine does not induce CYP 1A2, 2C19, or 3A4/5. Use with other medications with caution.

Can be taken with or without food.

Azacitidine can cause fetal harm during pregnancy. Avoid use in pregnant women. Females of reproductive potential should use effective contraception during treatment and for 6 months after the last dose.

It is unknown if azacitidine is excreted in human milk. Avoid use in nursing mothers.

Safety and efficacy in pediatric patients have not been established.

No specific dose adjustment is needed for elderly patients.

• Caution in mild to moderate renal impairment
• Dose adjustment may be needed in severe renal impairment
• Caution in hepatic impairment

Overdose may cause excessive platelet count increase and thrombotic complications. No specific antidote.

Store below 30°C, away from light and moisture.

Azacitidine (C₈H₁₂N₄O₅)